Académique Documents
Professionnel Documents
Culture Documents
world wide. In the United States, it has been adopted by the American Joint Cancer Commission (AJCC) for sarcoma
staging and by the College of American Pathologists (CAP) Cancer Protocols for bone and soft tissue sarcomas. This
common lexicon is critical for the performance of clinical trials, which are increasingly international in scale, and for
translational research to be comparable. The WHO system helps to assure doctors and researchers that we are on the
same diagnostic page in such undertakings.
The fourth edition of the WHO Classification of Tumours of Soft Tissue and Bone blue book was published in February
2013. The new book surpasses the previous edition of the book published in 2002 in regards to its number of pages,
illustrations, and authors. In all, 159 authors from 24 different countries contributed to this book. Eleven of them are the
members of IARC/WHO committee for the International Classification of Diseases for Oncology (ICD-O). The editors of this
volume are Christopher D.M. Fletcher (soft tissue), Pancras C.W. Hogendoorn (bone), Fredrik Mertens and Julia Bridge
(genetics).
"In keeping with the rapidly increasing knowledge and the extensive studies of the genetics of tumours that took place
over the past decade, the new book has incorporated more detailed cytogenetic and molecular data."
Of the major modifications made to the previous edition is the addition of three new chapters (gastrointestinal stromal
tumours, nerve sheath tumours and undifferentiated high-grade pleomorphic sarcoma of bone).
In keeping with the rapidly increasing knowledge and the extensive studies of the genetics of tumours that took place over
the past decade, the new book has incorporated more detailed cytogenetic and molecular data.
The grading of soft tissue tumours has always been a controversial issue. While the WHO does not strictly state a
preference in grading systems, one of the major modifications that have been made to the current WHO classification is
the designation of two distinct types of intermediate malignancy in terms of biological potential: the "locally aggressive"
and the "rarely metastasizing."
The authors acknowledged the poorly defined nature of malignant fibrous histiocytoma, MFH, (also known as UPS,
undifferentiated pleomorphic sarcoma) and haemangiopericytoma (now considered within the spectrum of solitary fibrous
tumor).
With the current advances in molecular and genetic studies, a subset of tumours has been moved into new sections
including angiomatoid MFH and extraskeletal myxoid chondrosarcoma which were reclassified under "Tumours of Uncertain
Differentiation." Multiple entities were newly recognized, and a few entities belonging to tumours of skin were also added
to this book. A few entities that were found to probably represent morphologic variants of other tumours were deleted
from the current classification and subsumed into other sections.
What follows is a series of brief highlights of this new WHO edition from each section of the soft tissue and bone sections.
Malignant
Dedifferentiated liposarcoma
Myxoid liposarcoma
Pleomorphic liposarcoma
Liposarcoma, not otherwise specified
General Changes
The current classification no longer includes mixed-type liposarcoma. Cases previously diagnosed as mixed-type
liposarcoma were almost always discovered to fall within a specific type of liposarcoma when subjected to molecular and
genetic testing. Myxolipoma was also deleted from the current classification. Most of the so-called myxolipomas are now
considered variants of spindle cell lipoma. Diffuse lipoblastoma is now the preferred term for lipoblastomatosis.
1. adipocytic (lipoma-like)
2. sclerosing
3. inflammatory types
A description of spindle cell liposarcoma still appears in the text. The lack of MDM2 immunopositivity or 12q15
amplification in this tumor type suggests spindle cell liposarcoma represents a separate group.
Dedifferentiated liposarcoma
The new addition to this liposarcoma type is the recognition of the rare situation in which the high grade (dedifferentiated)
component shows lipoblastic differentiation and resembles pleomorphic liposarcoma. This phenomenon has been referred
to as homologous lipoblastic differentiation or pleomorphic liposarcoma-like features.
Malignant
Adult fibrosarcoma
Myxofibrosarcoma
Low-grade fibromyxoid sarcoma
Sclerosing epithelioid fibrosarcoma
Nodular fasciitis
The identification of MYH9-USP6 gene fusion as a recurrent event in nodular fasciitis has confirmed its previously
controversial neoplastic nature.
The malignant counterpart of so-called fibrohistiocytic tumours, formerly known as malignant fibrous histiocytoma and its
subtypes was renamed undifferentiated sarcoma and reclassified under the undifferentiated / unclassified sarcomas
section described further below.
Smooth-muscle tumours
Benign
Leiomyoma of deep soft tissue
Malignant
Leiomyosarcoma (excluding skin)
Leiomyosarcoma
Cytogenetic analysis of several gene-expression profiling datasets identified multiple molecular subgroups of
leiomyosarcoma, including a muscle-enriched subtype and less differentiated group with varying prognoses. Some
tumours classified as UPS cluster closely with a subset of leiomyosarcoma suggesting the existence of dedifferentiated
leiomyosarcoma.
Myofibroma and myofibromatosis were reclassified under myopericytoma instead of fibroblastic / myofibroblastic tumours.
Skeletal-muscle tumours
Rhabdomyoma
Embryonal rhabdomyosarcoma
Alveolar rhabdomyosarcoma
Pleomorphic rhabdomyosarcoma
Spindle cell / Sclerosing rhabdomyosarcoma
Spindle cell / Sclerosing rhabdomyosarcoma was felt to now be well enough recognized and defined to be added to this
group.
Vascular tumours
Benign
Haemangioma
Synovial
Venous
Arteriovenous haemangioma / malformation
Epithelioid haemangioma
Angiomatosis
Lymphangioma
Malignant
Epithelioid haemangioendothelioma
Angiosarcoma of soft tissue
Pseudomyogenic (epithelioid sarcoma-like) haemangioendothelioma was added to the intermediate (rarely metastasizing)
subgroup.
Two intermediate vascular neoplasms that the Working Group had previously considered for inclusion in the 2002
classification, namely giant cell angioblastoma and polymorphous haemangioendothelioma, were not added to the current
classification due to the limited number of reported cases and lack of sufficient data. Recently, epithelioid
hemangioendothelioma has also been shown to be associated with a WWTR1-CAMTA1 translocation.
This chapter is a major and important addition to the new book. In the current classification, the benign category of GIST
corresponds to the AFIP prognostic groups 1, 2 and 3a. The uncertain malignant potential category corresponds to group
4, and the malignant category corresponds to groups 3b, 5, 6a and 6b.
Malignant
Malignant peripheral nerve sheath tumour
Epithelioid malignant nerve sheath tumour
Malignant Triton tumour
Malignant granular cell tumour
Ectomesenchymoma
This chapter was added to the new book. It was previously included with the 2007 WHO classification of tumours of the
central nervous system. The current WHO classification included tumours previously classified under cranial and peripheral
nerves, head and neck and skin tumours. This represents an important initiative to present the diverse family of
mesenchymal tumors into a single reference source. The 2007 classification did not include the following:
Ectomesenchymoma
Malignant
Synovial sarcoma NOS
Synovial sarcoma, spindle cell
Synovial sarcoma, biphasic
Epithelioid sarcoma
Alveolar soft-part sarcoma
Clear cell sarcoma of soft tissue
Extraskeletal myxoid chondrosarcoma
Extraskeletal Ewing sarcoma
Desmoplastic small round cell tumour
Extra-renal rhabdoid tumour
Neoplasms with perivascular epithelioid cell differentiation (PEComa)
PEComa NOS, benign
PEComa NOS, malignant
Intimal sarcoma
Malignant mesenchymoma is not included in the current classification. Most cases of malignant mesenchymoma reported
previously probably represent heterologous line of differentiation in specific sarcomas such as myxoid liposarcomas with
cartilaginous metaplasia, ALT and dedifferentiated liposarcomas with osseous, cartilaginous, smooth muscle or skeletal
muscle elements, MPNST with heterologous components and others.
This chapter was added to encompass a group of malignant tumours that were previously included in the fibrohistiocytic
tumours, namely malignant fibrous histiocytomas. These tumours lack a specifically identified line of differentiation
when analyzed by presently available technology. Dedifferentiated types of specific sarcomas are not included in this
category. Undifferentiated/unclassified sarcomas account for up to 20% of all sarcomas and about a quarter of these are
radiation-associated tumours. These tumours do not have distinct clinical or morphological characteristics that would
otherwise place them under specific types of sarcomas. Genetic subgroups, however, are emerging within this family and
this important work is ongoing.
In this group, EWSR1 is involved in non-ETS fusions with genes such as PATZ1, POU5F1, SMARCA5, NFATC2 or SP3.
Another recurrent rearrangement involves CIC-DUX4 fusion gene resulting in the chimeric CIC-DUX4 protein which
upregulates genes of the PEA3 subclass of ETS family.
It remains to be seen whether these cases represent one or more separate entities, or whether they are better classified
as variants of Ewing sarcoma.